ABSTRACT Down syndrome (DS) is caused by an extra copy of chromosome 21, which results in a wide variety of outcomes including unique facial features, medical vulnerabilities, and intellectual disability. It also results in premature aging processes and a high risk for Alzheimer's dementia (AD), both associated with cognitive decline. One crucial goal of research on DS is to understand the developmental course of cognitive decline, including when (or at what age) declines in various cognitive functions begin. This knowledge would open the door to early pharmaceutical, behavioral, or environmental interventions designed to slow the progression of early aging and AD in this population. The broad, long-term objective of the proposed project is to identify early cognitive decline in youth with DS during late adolescence into early adulthood. The proposed 3-year longitudinal study will enroll participants with DS aged 15-25 years. This age period is just before the age when cognitive decline becomes apparent in some functions in healthy neurotypical adults. Further, amyloid evidence suggests that this age period may very well align with the preclinical stage of AD in the DS population. Participants will complete a battery of cognitive and behavioral measures three times spaced at 18- month intervals, for a span of three years. The measures either (a) have been linked to AD progression in older adults with DS (e.g., Krinsky-McHale, Devenny, & Silverman, 2002) or (b) have been documented recently as declining during this age period (Conners, Tungate, Abbeduto, Merrill, & Faught, 2018). Syndrome specificity will be assessed by comparing participants with DS to participants with non-DS intellectual disability matched on age and nonverbal ability. Also, a variety of covariates will be measured to further enhance interpretation of developmental trends. Aim 1 is to identify early cognitive decline (episodic memory, executive function, phonological memory, expressive vocabulary, receptive grammar); Aim 2 is to identify changes in other domains that are related to aging and/or progression toward AD (e.g., adaptive behavior, maladaptive behavior, gait, and psychomotor speed); Aim 3 is to link observed cognitive and behavioral changes to symptoms of MCI (e.g., everyday orientation, concentration, basic functioning) as measured by instruments such as the Modified Mini-Mental State Exam. The proposed study will move the field forward by identifying developmental trends (especially declines) in a unique age range in DS across a broad array of measures. Future directions include extending the longitudinal time frame and adding amyloid/tau measures to better interpret declines as AD-related or not.